The Neuropathology Core is based at the USC Health Sciences Campus, with a Sub-Core at UC Irvine and a vascular dementia tissue repository at Rancho Los Amigos Hospital (RLAH). During the past 5 years, tissue needs of over 100 investigators were met. Projected use over the next years includes over 120 investigators. Each site has a complementary but distinct overall focus: USC serving a broad spectrum of projects based on molecular and cellular system changes in AD; UCI emphasizing neural plasticity of the limbic system and the role of amyloid in neurodegeneration in AD; and the evaluation of vascular dementia at RLAH. With diagnostic studies and research performed at all three sites, Neuropathology Core repathologic diagnosis, preservation and distribution of postmortem tissues to investigators throughout the ADRC, data management and the performance of Core research projects. All three sites continue to participate with the CERAD program to establish a standardized, reliable diagnostic protocol obtained by national consensus among neuropathologist. The Core provides twenty-four hour neuropathology services to assure the availability of CNS and somatic tissues that are prepared with minimum postmortem delay. Tissues are prepared according to the autopsy protocol described in our CNS dissection manual. At USC and UCI, tissue will be available from a highly selected clinical population yielding a combined total of approximately 80 to 90 AD and control cases per year for distribution. Vascular dementia tissues from at least 18 patients will be obtained annually at RLAH. Effects of therapeutic interventions initiated in the Clinical Core, including those carried out in the Pharmacology subcore, are monitored for histopathologic changes that may be retrospectively correlated with severity of dementia and other diagnostic parameters. Core projects include the development and molecular characterization of diagnostic probes in CNS tissues and CSF of AD patients. Our neuropathology database system stores autopsy information, keeps inventory information and links with data obtained in the clinical core. Further integration and ease of data access to investigators will be developed in conjunction with the Teradata project over the next grant period.